title: Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson's disease with moderate neurodegeneration.
abstract: The protective impact of exercise on neurodegenerative processes has not been confirmed, and the mechanisms underlying the benefit of exercise have not been determined in human Parkinson's disease or in chronic animal disease models. This research examined the long-term neurological, behavioral, and mechanistic consequences of endurance exercise in experimental chronic parkinsonism. We used a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease with moderate neurodegeneration and examined the effects of treadmill exercise on movement and balance coordination, changes in dopamine neuron biomarkers, mitochondrial functions, and neurotrophic factor activities in the nigrostriatal system. The exercise results were compared with those of the control and sedentary chronic parkinsonian animals. After 18 weeks of exercise training in the chronic parkinsonian mice, we observed a significant deterrence in the loss of neuronal dopamine-producing cells and other functional indicators. The impaired movement and balance incoordination in the chronic parkinsonian mice were also markedly reduced following exercise. Mechanistic investigations revealed that the neuronal and behavioral recovery produced by exercise in the chronic parkinsonian mice was associated with an improved mitochondrial function and an increase in the brain region-specific levels of brain-derived and glial cell line-derived neurotrophic factors. Our findings indicate that exercise not only produces neuronal and mitochondrial protection, it also boosts nigrostriatal neurotrophic factor levels in the chronic parkinsonian mice with moderate neurodegeneration. Therefore, modifying lifestyle with increased exercise activity would be a non-pharmacological neuroprotective approach for averting neurodegenerative processes, as demonstrated in experimental chronic parkinsonism.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA. ylau2@uh.edu
authors.forename: Yuen-Sum
authors.initials: YS
authors.lastname: Lau
authors.forename: Gaurav
authors.initials: G
authors.lastname: Patki
authors.forename: Kaberi
authors.initials: K
authors.lastname: Das-Panja
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Le
authors.forename: S Omar
authors.initials: SO
authors.lastname: Ahmad
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015444:Exercise; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000503:physiopathology*; D010805:Physical Conditioning, Animal; D011339:Probenecid / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000277:Adjuvants, Pharmaceutic; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D051098:Glial Cell Line-Derived Neurotrophic Factors; D013482:Superoxide Dismutase; D011339:Probenecid; D004298:Dopamine